The stomach is the gateway

Absorption and Metabolism of L‐Dopa by the  Stomach

L. Rivera-Calimlim

C. A. Dujovne

J. P. Morgan

Louis Lasagna

J. R. Bianchine

ABSTRACT The absorption and gastric metabolism of L-dopa (L-dihydroxyphenylalanine) were studied in 14 Parkinsonian patients. Patients were given p. o. 25 μCi (500 mg) 14C L-dopa labelled at the β-carbon mixed with 2 g polyethylene glycol as a dilution marker. Absorption was evaluated by determining the gastric rate of absorption, gastric clearance, serum levels, and urinary excretion of 14C. L-dopa and its metabolites in the gastric juice and serum were fractionated by column chromatography. Patients with gastric juice pH of 1.2-2.1 had a gastric rate of absorption of 62.6±4.7 mg/h with a gastric clearance of 31.7.4.1 ml/h. The gastric emptying time was 228±96min. 17.2–26.4% of total radioactivity in the gastric juice were dopa metabolites. Patients with gastric pH of 6.9-7.2 had a very rapid emptying time (an average of 22 min.) with no gastric absorption. The amount of metabolites in their gastric juice was insignificant. Gastric absorption and emptying time were reduced in patients when the gastric pH was raised to 3.5-4.5 with antacids. Serum peak concentrations were higher and more rapidly achieved in patients with high gastric pH than in those with low pH.The most rapidly achieved and highest serum peak levels were observed in patients with partial gastrectomy and in those who were given the drug by duodenal infusion. It appears that direct absorption of L-dopa by the stomach may be limited by gastric metabolism of the drug, a possibility supported by the study in vitro of human stomach tissue obtained at surgery. The inverse relationship between the gastric emptying time and serum levels suggests that the intestine is the major site of L-dopa absorption. Thus factors that prolong gastric emptying time may lower serum levels of L-dopa by delaying access of the drug to the site of absorption and by increasing metabolism before absorption.

August 12, 2014 - Posted by Chris | Anatomy-gut, Medication, Research